title: Hox genes define distinct progenitor sub-domains within the second heart field.
abstract: Much of the heart, including the atria, right ventricle and outflow tract (OFT) is derived from a progenitor cell population termed the second heart field (SHF) that contributes progressively to the embryonic heart during cardiac looping. Several studies have revealed anterior-posterior patterning of the SHF, since the anterior region (anterior heart field) contributes to right ventricular and OFT myocardium whereas the posterior region gives rise to the atria. We have previously shown that Retinoic Acid (RA) signal participates to this patterning. We now show that Hoxb1, Hoxa1, and Hoxa3, as downstream RA targets, are expressed in distinct sub-domains within the SHF. Our genetic lineage tracing analysis revealed that Hoxb1, Hoxa1 and Hoxa3-expressing cardiac progenitor cells contribute to both atria and the inferior wall of the OFT, which subsequently gives rise to myocardium at the base of pulmonary trunk. By contrast to Hoxb1(Cre), the contribution of Hoxa1-enhIII-Cre and Hoxa3(Cre)-labeled cells is restricted to the distal regions of the OFT suggesting that proximo-distal patterning of the OFT is related to SHF sub-domains characterized by combinatorial Hox genes expression. Manipulation of RA signaling pathways showed that RA is required for the correct deployment of Hox-expressing SHF cells. This report provides new insights into the regulatory gene network in SHF cells contributing to the atria and sub-pulmonary myocardium.
authors.affiliation: Laboratoire de Génétique Médicale et Génomique Fonctionnelle, Inserm UMR_S910, Université d'Aix-Marseille, 27 Bd Jean Moulin, 13005 Marseille, France. nicolas.bertrand@univmed.fr
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bertrand
authors.forename: Marine
authors.initials: M
authors.lastname: Roux
authors.forename: Lucile
authors.initials: L
authors.lastname: Ryckebüsch
authors.forename: Karen
authors.initials: K
authors.lastname: Niederreither
authors.forename: Pascal
authors.initials: P
authors.lastname: Dollé
authors.forename: Anne
authors.initials: A
authors.lastname: Moon
authors.forename: Mario
authors.initials: M
authors.lastname: Capecchi
authors.forename: Stéphane
authors.initials: S
authors.lastname: Zaffran
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000172:deficiency / Q000235:genetics; D000818:Animals; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D019070:Cell Lineage; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D005318:Fetal Heart / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008955:Models, Cardiovascular; D011247:Pregnancy; D015398:Signal Transduction; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism; D000099261:Homeobox A1 Protein
chemical_list: D000445:Aldehyde Oxidoreductases; D018398:Homeodomain Proteins; D014157:Transcription Factors; D014212:Tretinoin; D000099261:Homeobox A1 Protein; C101121:HOXB1 homeodomain protein; C080331:Hoxa3 protein, mouse; C470579:RALDH2 protein, mouse